2f3x

<StructureSection load='2f3x' size='340' side='right' caption='[[2f3x]], [[Resolution|resolution]] 3.10&Aring;' scene=''>

<table><tr><td colspan='2'>[[2f3x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"vibrio_subtilis"_ehrenberg_1835 "vibrio subtilis" ehrenberg 1835]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F3X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2F3X FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MLC:MALONYL-COENZYME+A'>MLC</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2f41|2f41]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fapR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1423 "Vibrio subtilis" Ehrenberg 1835])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2f3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3x OCA], [http://pdbe.org/2f3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2f3x RCSB], [http://www.ebi.ac.uk/pdbsum/2f3x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2f3x ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/FAPR_BACSU FAPR_BACSU]] Transcription factor involved in regulation of membrane lipid biosynthesis by repressing genes involved in fatty acid and phospholipid metabolism. Binds to the 5'-TTAGTANNNNNTANTAA-3' consensus sequence found in the promoter of fabHAF operon (containing fabHA and fabF genes), yhdO and fapR genes and prevents their expression. Its action is probably modulated by malonyl-CoA.<ref>PMID:12737802</ref>

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== Publication Abstract from PubMed ==

Malonyl-CoA is an essential intermediate in fatty acid synthesis in all living cells. Here we demonstrate a new role for this molecule as a global regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro transcription and binding studies, we demonstrate that malonyl-CoA is a direct and specific inducer of Bacillus subtilis FapR, a conserved transcriptional repressor that regulates the expression of several genes involved in bacterial fatty acid and phospholipid synthesis. The crystal structure of the effector-binding domain of FapR reveals a homodimeric protein with a thioesterase-like 'hot-dog' fold. Binding of malonyl-CoA promotes a disorder-to-order transition, which transforms an open ligand-binding groove into a long tunnel occupied by the effector molecule in the complex. This ligand-induced modification propagates to the helix-turn-helix motifs, impairing their productive association for DNA binding. Structure-based mutations that disrupt the FapR-malonyl-CoA interaction prevent DNA-binding regulation and result in a lethal phenotype in B. subtilis, suggesting this homeostatic signaling pathway as a promising target for novel chemotherapeutic agents against Gram-positive pathogens.

Structural basis of lipid biosynthesis regulation in Gram-positive bacteria.,Schujman GE, Guerin M, Buschiazzo A, Schaeffer F, Llarrull LI, Reh G, Vila AJ, Alzari PM, de Mendoza D EMBO J. 2006 Sep 6;25(17):4074-83. Epub 2006 Aug 24. PMID:16932747<ref>PMID:16932747</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 2f3x" style="background-color:#fffaf0;"></div>

[[Category: Vibrio subtilis ehrenberg 1835]]

[[Category: Alzari, P M]]

[[Category: Buschiazzo, A]]

[[Category: Guerin, M E]]

[[Category: Hot-dog fold - malonyl-coa complex]]

[[Category: Gene regulation]]